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Abstract
Smart metabolic metro-map refers to a dynamically stimulable model of the metabolic pathways. F. Hoffmann-La Roche Ltd provides a static version of the biochemical pathways.
A static biochemical pathways map is a good guideline to understand the general functions and connections. It is however not sufficient to capture the time dependencies of the biochemical interactions.
We are developing a stimulable electrical model predictive of the flow of the forward and backward reactions in time domain when a defect on a pathway is present.
In the case of rare metabolic disorder, the dysfunctional enzyme results in a partial forward reaction as well a partial backward reaction. The backward signaling results in substrate accumulation in the previous step. This in turn induces another partial backward reaction. The sum of these time dependent behavior creates a continuous backward signal. The induced backward signal is a crucial consideration which could predict the rate of accumulation and congestions of the defective pathways.
In the case of a defect on a pathway, periodic stimulation of the biochemical pathways results in a periodic accumulation of the intermediate metabolites. The peak (maximum) point of accumulation causes the acute phase of a disease.
An electrical software model of the biochemical pathways is constructed to be able to simulate scenarios with several metabolic excitations simultaneously or sequentially. The model is excitable by launching user-defined electrical signals at specified input ports.
We use periodic and non-periodic electrical signals to illuminate the pathway and to detect the congestion on a pathway , following the backward signal flow and its interaction with an incoming signal. These interactions are illuminated using high-end visualization techniques and CAD models.
We developed a technique to effectively identify the triggers and subdue the acute attacks of a defect of heme biosynthesis in 3 members of a family with a defect on CPOX gene.
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